All Publications

  • Lola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development. Nature communications Ramalingam, V., Yu, X., Slaughter, B. D., Unruh, J. R., Brennan, K. J., Onyshchenko, A., Lange, J. J., Natarajan, M., Buck, M., Zeitlinger, J. 2023; 14 (1): 5862


    While the accessibility of enhancers is dynamically regulated during development, promoters tend to be constitutively accessible and poised for activation by paused Pol II. By studying Lola-I, a Drosophila zinc finger transcription factor, we show here that the promoter state can also be subject to developmental regulation independently of gene activation. Lola-I is ubiquitously expressed at the end of embryogenesis and causes its target promoters to become accessible and acquire paused Pol II throughout the embryo. This promoter transition is required but not sufficient for tissue-specific target gene activation. Lola-I mediates this function by depleting promoter nucleosomes, similar to the action of pioneer factors at enhancers. These results uncover a level of regulation for promoters that is normally found at enhancers and reveal a mechanism for the de novo establishment of paused Pol II at promoters.

    View details for DOI 10.1038/s41467-023-41408-1

    View details for PubMedID 37735176

  • The dynseq browser track shows context-specific features at nucleotide resolution. Nature genetics Nair, S., Barrett, A., Li, D., Raney, B. J., Lee, B. T., Kerpedjiev, P., Ramalingam, V., Pampari, A., Lekschas, F., Wang, T., Haeussler, M., Kundaje, A. 2022

    View details for DOI 10.1038/s41588-022-01194-w

    View details for PubMedID 36241719

  • Acquisition of innate odor preference depends on spontaneous and experiential activities during critical period. eLife Qiu, Q., Wu, Y., Ma, L., Xu, W., Hills, M., Ramalingam, V., Yu, C. R. 2021; 10


    Animals possess an inborn ability to recognize certain odors to avoid predators, seek food and find mates. Innate odor preference has been thought to be genetically hardwired. Here we report that acquisition of innate odor recognition requires spontaneous neural activity and is influenced by sensory experience during early postnatal development. Genetic silencing of mouse olfactory sensory neurons during the critical period has little impact on odor sensitivity, discrimination, and recognition later in life. However, it abolishes innate odor preference and alters the patterns of activation in brain centers. Moreover, exposure to an aversive odor during the critical period abolishes aversion in adulthood in an odor-specific manner. The loss of innate aversion is associated with broadened projection of OSNs. Thus, a delicate balance of neural activity is required during the critical period in establishing innate odor preference and ectopic projection is a convergent mechanism to alter innate odor valence.

    View details for DOI 10.7554/eLife.60546

    View details for PubMedID 33769278

  • TATA and paused promoters active in differentiated tissues have distinct expression characteristics MOLECULAR SYSTEMS BIOLOGY Ramalingam, V., Natarajan, M., Johnston, J., Zeitlinger, J. 2021; 17 (2): e9866


    Core promoter types differ in the extent to which RNA polymerase II (Pol II) pauses after initiation, but how this affects their tissue-specific gene expression characteristics is not well understood. While promoters with Pol II pausing elements are active throughout development, TATA promoters are highly active in differentiated tissues. We therefore used a genomics approach on late-stage Drosophila embryos to analyze the properties of promoter types. Using tissue-specific Pol II ChIP-seq, we found that paused promoters have high levels of paused Pol II throughout the embryo, even in tissues where the gene is not expressed, while TATA promoters only show Pol II occupancy when the gene is active. The promoter types are associated with different chromatin accessibility in ATAC-seq data and have different expression characteristics in single-cell RNA-seq data. The two promoter types may therefore be optimized for different properties: paused promoters show more consistent expression when active, while TATA promoters have lower background expression when inactive. We propose that tissue-specific genes have evolved to use two different strategies for their differential expression across tissues.

    View details for DOI 10.15252/msb.20209866

    View details for Web of Science ID 000624493600002

    View details for PubMedID 33543829

    View details for PubMedCentralID PMC7863008